Survivor Guilt

Roughly fourteen months ago, as I flew to Houston for a consult with a surgeon at MD Anderson, I found out another Cushing’s patient had just had her surgery in the same place.  She had the same endocrinologist as me and the same surgeon.  I had been following her case with much interest, as she was a few steps ahead of me in the process and I hoped to get some sense of what was to come for me by following her progress.

I didn’t know much about this patient at this point beside some basic information.  She lived very far from me, she had a family and I knew she had had Cushing’s for a very long time.  She was a regular member on the Cushing’s Help boards that I had recently joined and had lots of advice for us newbies on testing and symptoms.   And now, she was literally a mile away from me, recovering in a hospital bed after having the same surgery I was about to have myself.  It was such a strange experience hearing about her post-op surgery experience that week.  As I would later discover is very typical for her, she was even offering helpful tips for other pre-op patients from her hospital room.

It was during this time, I connected with this patient and we went from being two patients to two friends.  We were in constant contact during recovery, sharing the details of how we were feeling, what our bodies were going through, our fears and our frustrations.  We are still in contact every day.  I have had the opportunity to learn about her family, I have met her husband, I have hugged her.

Even though we had exactly the same diagnosis, the same doctors, the same procedure, in the weeks following our respective surgeries it was clear we were heading down different paths.  While I had clear signs of remission – I was sleeping at night, my “brain fog” was gone, I had trouble weaning off replacement steroids – the initial signs were that my friend was not in remission.  She was able to wean herself off replacement steroids very quickly and many of the troubling signs of Cushing’s had not disappeared after surgery.   It was devastating.

Through all of this, she kept a stiff upper lip.  She shared her experiences with other patients so they could learn from what was happening to her.  She encouraged and cheered for me and the patients that had surgery and recovered in the ensuing months.  And she kept trying to sort out what to do about her own situation at the same time.  She handled the whole thing with grace, as I would learn is her way with pretty much everything.

The whole thing made me feel terrible (poor me!!).  It felt so wrong that this lovely woman had suffered so long only to find out the surgery didn’t work and she would likely have a long road ahead of her to get better.  And here I was, dealing with Cushing’s intensely for about a year, waltzing in for surgery and waltzing out.  I had a serious case of survivor guilt.   It just didn’t feel right that we both didn’t get better.  And if anyone was going to stay sick, it should have been me.  She did her time.  Compared to what she went through?  What happened to me was nothing.

A full year later, we are both struggling.  She is now dealing with growth hormone deficiency, a potential complication from pituitary surgery.  I am dealing with…well, whatever my crap is.  As perverse as it sounds, I feel a little better knowing I am still in the trenches with her.   We aren’t quite fighting the same battle anymore, but at least I don’t feel like I left my fellow soldier on the field.  Hopefully a year from now, we will be sitting around a campfire somewhere, swapping battle stories and more importantly talking about all the fun and wonderful things we are doing now that the war is over.

Plan D, Part I: Genetic Testing

After learning I would not be receiving any further help from the oncologist or my PCP figuring out what is going on, I had to move on to my next plan of attack.   For a variety of reasons – including the obvious reason that I am very symptomatic and had a suspicious Octreoscan finding from January – there is no way I can just give up.   My current plan is to try and gather some more hard evidence and then, with the help of the Wizard, try again with another specialist.

I am getting very impatient waiting for the results of the genetic test to come back from the NIH.   If I do have MEN-1, I am most likely a “sporadic” case (i.e., I don’t have a clear family history of MEN-1).   I already know that roughly 40 percent of clinically confirmed sporadic cases do not end up with a positive genetic test.  But I would like to know for sure.  In the event I do have a positive genetic test, it would certainly speed things up.  The NIH informed me in January that the test would take three to six months to come back and I am just hitting the three month mark now.   So, I decide to go and see a geneticist myself to talk about the test and perhaps order one privately as well.

I was very glad M and I went to see the geneticist.  He took a very thorough history.  I told him what had been going on over the past few years and didn’t even really get into the details of the last few months when he put his pen down and paused for a moment before saying:  “Your chest.  You have a big red spot in the middle of your chest.  Does your chest get red like this often?”   Of course I said “YES!” and proceeded to tell him what had been going on.  He responded with “There are neuroendocrine tumors called carcinoids.  I think you might have one.  You need to get this looked into and soon.”  I wanted to run around the other side of the man’s desk and hug him.

He finished taking my history and was simultaneously impressed with what I had managed to figure out on my own through my various efforts and horrified that despite the fact something was obviously and horribly wrong, it had managed to get dismissed by so many doctors.   It turns out this particular geneticist tends to get a lot of difficult cases and he clearly enjoyed these cases.   Music to my ears at this point!

I received a formal dictation from him in the mail by the end of the week, with the following conclusion:  “There is an indisputable need to exclude multiple endocrine neoplasia type I and if necessary, type II, and for this purpose I obtained your blood sample for sequencing and deletion/duplication analysis.  If results are negative, consideration will be required for other possibilities including a polyendocrine inherited disorder.  I am willing to work with you until we can solve your troubling issues.  This may require further visits.”

You have no idea how much those last two sentences meant to me.  This is all I ask.   A couple of intelligent and caring doctors to work with me to chase this down until we figure it out one way or the other.  I already have my endocrinologist, the Wizard.  Now I have the geneticist too.   We WILL figure this out.  They are not going to give up on me when the going inevitably gets tougher.  I am starting to feel a little hopeful we might actually crack the case reasonably soon.

Of course, as luck would have it, I get a call from a genetic counsellor at the NIH later the same day. My genetic test for MEN-1 came back negative.  He was very happy to deliver this reassuring news to me, but as I explained to him at this point I had bittersweet feelings about the news.  MEN-1 is a very scary diagnosis, and we both agree that it would be a life-changing diagnosis.  On the other hand, I am sick and I can’t get treatment for whatever is wrong (and in my mind, MEN-1 is still the most likely candidate) until I know what it is.   The negative test result therefore doesn’t help us figure out what IS wrong.   The genetic counsellor confirmed that the genetic test does miss a large percentage of sporadic cases and that although a positive result can definitively confirm MEN-1, a negative result cannot rule it out.

Furthermore, after an extended conversation about what was going on with me, the genetic counsellor revealed that the NIH did not run the “full” genetic test on me.  The genetic test that was conducted was for the sequencing only – not the deletion and duplication analysis.  Sequencing is similar to looking for spelling mistakes (e.g., the letter “G” should never follow the letter “Z”).  It doesn’t pick up cases where whole pieces of code have been duplicated or are missing.  He told me that because suspicion for MEN-1 was low, they decided not to do the full genetic test but that if I did end up getting diagnosed with MEN-1 clinically, I should let them know and they would run the duplication and deletion analysis.   Grrrr…..  Needless to say, I was glad I did my own “audit” of the genetic test and saw a geneticist on my own.  And maybe it won’t make any difference at all that only the sequencing was performed.  But to me, it still highlights the importance of asking questions and fully understanding exactly what tests have been run and what they mean.  Had I not asked a million questions and pushed back with the genetic counsellor, I would not have received this information on the phone.

I should have the results of the second genetic test back in two weeks.  I am fully expecting the results to come back negative, given the negative findings from the NIH and the high proportion of negative tests for sporadic cases in general.  However, I will still rest easier knowing that I did everything possible to thoroughly investigate MEN-1 from the genetic side.  More importantly, I now feel I added a really valuable doctor to my team, one with an entirely different perspective and with some new thoughts on differential diagnoses as well.

A Second Wind

After struggling for breath for the last couple of months, I am finally getting some serious relief from a combination of hydrocortisone and Zyrtec.  Hydrocortisone (HC) is synthetic cortisol, a substance I have a love-hate relationship with after Cushing’s.  After getting out of the hospital about a month ago and starting an HC regime at home to try and keep the “carcinoid syndrome” symptoms (if that’s what they are) – breathing trouble, flushing, coughing – under control I was starting to feel like I was getting Cushing’s again. I started to get puffy, my buffalo hump started coming back and I started breaking out in acne again.  Been there, done that, don’t want to do it again.  I wanted to get off the HC as quickly as possible, but was facing the choice of living with the unpleasant side effects of the steroids or not being able to talk or move around without coughing and gasping for air.  Steroids were winning by a mile, but I was not happy about it.

After doing a bunch of online research and upon the recommendation of some carcinoid patients, I added anti-histamines to the mix.  Just as the tumors causing Cushing’s spit out ACTH or cortisol, other neuroendocrine tumors spit out serotonin and histamine.  As a result, plain old over-the-counter anti-histamines help a lot of patients manage their symptoms.  And, whoa, what a difference a little Zyrtec has made!  It has been nothing short of miraculous.  I am on 25% of the HC dose I was on a few weeks ago and am somewhat optimistic I will be able to get all the way off “the juice” by the end of the month.  What’s even better is that I can almost talk and move around normally.  If I get too excited or talk a fair amount, I still cough and flush.  But I can walk around the house, do a few things outside, and finish complete sentences.  Last night, I even went to a movie with M and a friend and managed to get there and back and actually talk a little without turning into a purple, wheezing mess.  Just trying to get dressed to leave the house last week would have done me in.   Now, I feel like a living, breathing human being again and not like a caged animal.

Now that I have a drug combo that is making my life tolerable, my sense of optimism is coming back too.   I don’t feel nearly as hopeless as I have been feeling over the past few weeks.  I really think I am getting close to figuring this out.  Scratch that.  I think I figured it out in January and I have at least convinced the Wizard another neuroendocrine tumor might be my issue.  Now, I think I am close to getting someone else to DO something about it.   Instead of spending all my energies figuring out how to make it through the day, I have the second wind I need to implement Plan D.

Sleepless Nights with the Twins

One of the most annoying and universal symptoms of Cushing’s is sleepless nights.  When I was in the beginning stages of Cushing’s, I would start waking up earlier than my alarm by an hour or so – I would usually get up at 5am, but now I was wide awake at 4am.  Then 3:30am.  Eventually, it was 1:30am and at some point, I would not be able to fall asleep at all until around 5am.

Why does Cushing’s cause sleeplessness?  Cortisol is a steroid produced by the adrenal glands and it is essential for life.  It has a huge number of roles (there will be future blog posts on some of it’s other roles), but one of the roles it is best known for it’s role as a stress hormone.  Your body instructs the adrenal glands to secrete cortisol when it perceives you are facing some sort of threat.  If you ever thought you heard a suspicious noise in your house late at night and worried it was an intruder, that heightened sense of being alert and feeling ready to bolt at a second’s notice is partially due to cortisol.

In a healthy person, cortisol has a diurnal rhythm, as illustrated by the red line in the graph below.  Cortisol levels are very low overnight and start increasing right around the time you start waking up.  Cortisol peaks in the morning around 8am and then gradually decreases over the rest of the day, reaching it’s lowest point when it is time for you to go to bed.  And you thought it was just that pot of coffee you drink that was getting you up, showered, dressed and off to work in the mornings!  The pituitary gland, partially through it’s regulation of cortisol, is helping to get you up and going during the day and letting you sleep at night.

If you have Cushing’s, a tumor overrides your pituitary gland’s regulation of cortisol.  Tumors don’t have a diurnal rhythm, as illustrated by the blue line in the graph.  Tumors don’t care about what the pituitary gland is trying to do.  They just spit out hormones whenever they want.  As a result, Cushing’s patients often lose their diurnal rhythm.  Cortisol levels are high whenever the tumor decides they are going to be high.  Cushing’s is like having an intruder knocking things over in your house all night long.


The sleepless nights were really frustrating.  I tried all sorts of over-the-counter sleep medications and eventually a prescription one to try and get my body to shut off and sleep.  But nothing worked after awhile.   At some point, I just gave up and tried to find other ways to entertain myself during these long, wired nights.

Luckily for me, a friend of mine had twins not long after I stopped sleeping altogether on my bad nights.  While I don’t wish sleepless nights on anyone (including new mothers), it was a nice time for her and I to interact.   She and her husband were taking turns staying up for feedings and during her shift, we could chat over IM without waking anyone else up.   We could IM for hours while she fed and changed the twins.  It was a perfect way for each of us to have some company and talk about what was going on in her life and mine and I think for both of us it made those long nights a little more tolerable.

Unbeknownst to me at this time, I had my own set of twins.  My twins were delivered by a neurosurgeon about three months later.  Although my twins will never take their first steps, learn to say “Mommy” or cost me a fortune in college tuition, I am happy to report I have not had a single sleepless night since their birth.  Unfortunately, I cannot say the same for my friend.

Good Patients Are Good Auditors

In my former healthy life (and hopefully in my future healthy life), I was a litigation consultant.  I worked for a  firm full of PhD Economists and MBAs that provides economic analysis in the form of expert reports and testimony at trial in high profile lawsuits.  If you take a look at the Wall Street Journal on any given day, there is a good chance we are involved in the one of the cases on the front page.   Look around your house and I can almost guarantee I have worked on cases involving some of the products you use or the companies that make, market or sell them.

The work our firm does requires a great deal of attention to detail – not only because we want to make sure the job is done right on principle but also because there is a set of lawyers and consultants on the other side of the lawsuit that are going to dissect our work in great detail to try and find any sort of potential flaw in our analysis to bolster their case.  And so, for this reason, every important piece of analysis goes through a complete internal audit where a brand new team comes in and reviews every sentence, every source, every line of computer code to double and triple check the entire analysis.   The audit team and the team working on the original report, together, make sure the final work product is flawless.  This process is not in place because the original team is incompetent or untrustworthy – it is in place out of recognition of the fact that the team is made up of humans that completed a very complicated analysis under demanding time constraints.  Some angles or analyses may have been overlooked; some mistakes may have been made.  The audit process is time consuming and expensive but necessary to find those mistakes before the other side does.

As a patient, especially a patient with a rare and complicated disease like Cushing’s, it is important for the doctor and patient to work together in the same way.   Your doctor is the original team – planning and conducting the original analysis.  You are the auditor – going through each step of the completed analysis and double checking that the logic of the analysis passes the “sniff” test, that the numbers are correct and interpreted properly and that no stone was left unturned during the original analysis.  If you don’t serve as an auditor, you and your team could miss some very important mistakes.

I relearned this lesson over the course of the past two days as I reviewed some of my old medical records back from 2007.  Before the last few years, I didn’t audit anything.  I never even bothered to look at my lab results or even ask what labs my doctor ran.  I trusted my former endocrinologist completely.  Until very recently, it also never occurred to me that I had Cushing’s before the beginning of 2012.  So what I saw in my record shocked me.

As I look back through my records, I now see that as far back as May 2007, I was complaining of being very tired.  I had a known pituitary tumor since 2003 and my endocrinologist ordered follow-up MRIs every year to make sure it was stable.  I had some discharge from my breasts over the course of several years and my endocrinologist examined me, saw it for himself, sent me for a mammogram, and checked my prolactin.   As part of my initial work-up after joining his practice, he checked my growth hormone and found it was elevated.  We talked about the symptoms of excess growth hormone and he mentioned that your hands and feet can grow – and my feet HAD increased by a full size in the last few years.   My running shoe size (I have worn the same exact make and model of shoe for almost a decade) went up a size and a half.   I remember asking him whether this meant I might get a few inches taller too (that didn’t sound so bad!) and he laughed and told me just my feet would grow and that I would look like Ronald McDonald.

Given my odd labs, my breast discharge, my big feet, and my old pituitary MRIs, he ordered a few extra tests just to make sure everything was fine:  an overnight dexamethasone suppression test and a growth hormone suppression test.  The dexamethasone suppression test is a screening test for Cushing’s disease.  The growth hormone suppression test is a screening test for acromegaly.  Both disorders are caused by pituitary tumors that are secreting hormones- ACTH in the former case and growth hormone in the latter.

The suppression tests take advantage of the fact that tumors don’t respect the normal feedback loop of the pituitary gland.  A substance is administered (dexamethasone for the former test and glucose for the latter test) that in a healthy person is supposed to suppress the relevant hormone produced by the pituitary gland.   For example, after administering dexamethasone, a healthy pituitary gland will realize it should stop pumping out ACTH and cortisol levels will fall correspondingly.  If a tumor is producing ACTH, however, administering dexamethasone won’t result in a marked drop in cortisol because the tumor doesn’t care about the dexamethasone or what the rest of the pituitary gland wants to do.  It just keeps spitting out ACTH.   To make a long story short, the dexamethasone suppression test should indicate that cortisol levels are suppressed below a particular cut-off and the growth hormone suppression test should indicate that growth hormone levels are suppressed below a particular cut-off in healthy individuals.  If you don’t suppress on these tests?  You need to start checking to make sure you don’t have a pituitary tumor that is actively producing hormones.

Once the tests came back, he assured me during my follow-up that both tests came back normal and there was nothing to worry about.  I had been complaining of being tired on my current dose of thyroid meds and he was reluctant to increase the dose and told me it was probably the marathon training wearing me down and that I should try drinking more coffee (the last part is literally written into my chart).  As for my feet, we both chalked it up to possible design changes that Asics must have made to my favorite shoe.

This endocrinologist seemed super thorough to me – he ran all these tests, he ordered follow-up MRIs, he sent me for a mammogram.  So, it never even occurred to me that I should actually look at the test results or ask further questions.  I was tired, but I was working and running a lot and it’s probably normal to be wiped out from that.  So I drank more coffee and kept bringing it up with him in my appointments but we both concluded it probably was my lifestyle and not my thyroid making me tired, as my thyroid levels were pretty normal.

So imagine my surprise when I dusted off my old labs yesterday and today and discovered I failed to suppress on BOTH the dexamethasone test and the GH suppression test.  BOTH.  In 2007.  I am still trying to process this information.

I knew I failed to suppress on a dexamethasone test in 2013 and I had a heated argument with my endocrinologist at that time because he told me I did suppress on that test.  But in 2013, when it was completely obvious something was wrong, I looked up the cut-off and my lab values and found out he was using the wrong cut-off.  I sent him an email with the Endocrinology Guidelines laying out the proper cut-offs attached and pointed out that I had in fact FAILED to suppress on the 2013 test.  But by then, we were mad at each other and all he was willing to do was see me in his office in six weeks after refusing to order a follow-up MRI.  That was our last conversation.

When I had my final set of labs drawn at MD Anderson the day before pituitary surgery for Cushing’s in 2014, my IGF-1 was beyond the top of the reference range.  And I had really severe carpal tunnel syndrome at that point and noticed my tongue felt too big for my mouth as well.  So at this point, I already suspected my growth hormone might have been too high in addition to my ACTH.  But I am now much more suspicious that my two little pituitary tumors were probably producing both hormones – and that I wasn’t someone that just started getting rapidly sick in 2012 but had actually started getting sick as far back as at least 2007.

Cortisol Testing for Cushing’s: How to Catch a Sneaky Jerk in Action

Cushing’s can behave in one of two ways.  The first kind is called “florid” Cushing’s.  In this case, the tumor is a jerk all of the time.  He is busy pumping out ACTH or cortisol (depending on his location) at all times of the day.  Since this little guy has no sense of subtly he is relatively easy to catch – pretty much any time you test your cortisol, you are going to discover he is active and therefore your cortisol is abnormally high.

The second kind of Cushing’s is called “episodic” or “cyclic.”  In episodic cases, the tumor is a real sneaky little jerk.  He only spits out hormones once in awhile and although this sounds better in many ways than the florid jerks, it is a unique kind of hell in many other ways.  Episodic tumors put their host on a hormonal roller coaster, causing episodic patients to careen between “highs” from too much cortisol and “lows” from too little.   For me, during the “highs,” when my body had too much cortisol, I was often unable to sleep at all at night, my high blood pressure was really high (often 180/100 at night), and I had “‘roid rage.”   During the “lows,” when my body had too little cortisol, I felt like I had a bad flu – I was very nauseous, my joints and skin hurt, I had a fever, and was completely exhausted around the clock.  Every Cushing’s patient has their own slightly different set of high and low symptoms, but my particular set is pretty common.    And Cushing’s patients have cycles of different lengths as well.  Some patients stay in a “high” for a few weeks at a time.  My cycles were very short and pretty predictable.  For months and months, I was high for three days and then low for three.  Like clockwork.  Stop and imagine this for a moment:  every three days, for months, you get hit with what feels just like a stomach flu.  And then not being able to sleep during the other three days.   As I got sicker, my high periods got longer and my lows shorter (and more unpleasant), but the symptoms stayed roughly the same.  But the change in symptoms as I moved from high to low was undeniable – I often could tell you the hour I started going from a high to a low.  It was very striking.

In addition to the hormonal roller coaster, the other difficult part of having episodic Cushing’s is that it can be very hard to catch the little jerk in action.  Since the tumor is not pumping out hormones all the time, if you happen to test when he is active you will find your cortisol is abnormally high.  If you happen to test when he is inactive?  Your cortisol will be normal or,  as was often the case for me, abnormally LOW.

There are two schools of thought on when to test your cortisol if you have a sneaky jerk of a tumor.  The first is to figure out your high symptoms and test when you feel high.  The second is referred to by patients as  “marathon testing” which is essentially testing every day for a few weeks.   Being a very impatient person and because I cycled between highs and lows very fast, I decided to go the marathon route.  A calendar from my last month of testing is below.  I kept track of three things:  (1) my menstrual cycle, (2) whether I felt bad (i.e., low) or good (i.e., high), and (3) what kind of test I did and the test result.  Tests with an asterisk beside them indicate the cortisol level is above the upper limit of normal.

Here is what I learned:

1.  My symptoms did not always match my labs.  Even during stretches of days where I felt “high” I could have high cortisol one day and low cortisol the next.   So, for me?  Relying just on symptoms wasn’t reliable.  I am not claiming this is the case for everyone – this is how it worked for me.

2.  There are different kinds of cortisol tests – salivary, serum, and urinary free cortisol tests (UFC).  I never had a positive salivary or midnight serum test during this period.   UFC’s were the tests that demonstrated high cortisol for me.  I know from other patients that some patients always had high salivary test results but never high UFCs.  Or some had high midnight serums but never high salivary test results.  I want to come back and write a blog post about this later, because there is too much to say about why this happens.  Stay tuned.  The main takeaway is that you should try several different kinds of tests to see where high cortisol shows up in YOUR body.

3.  ALL of my high cortisol test results occurred during days 13 and 18 of my menstrual cycle.   Although this might sound like a coincidence?  It is not.  Several smart and helpful patients explained this to me and what they said was actually supported by my own testing.  Stay tuned for a blog post on this topic as well.

4.  Regardless of how and when you test, keep track of your symptoms and your test results in a spreadsheet or calendar.  If you are going to figure out how to catch your sneaky little jerk, tracking might help you keep tabs on the little guy.  Tracking was informative because, if nothing else, I learned points #1-#3 above.  That was useful for me!  I hope it is useful to you too.

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Cushing’s Awareness Day – Things I Learned from Cushing’s

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Today is Cushing’s Awareness Day – the birthday of Dr. Harvey Williams Cushing.  I am going to use this famous quote by Dr. Cushing as the inspiration for my post today and talk about what I learned from the experience of getting Cushing’s, in random order.

1.  Patients are smarter, more educated, and might play a bigger role in your survival than you can possibly imagine.

2.  Rare endocrine diseases, like Cushing’s, are hard to figure out.  The tumors can be hard to see and hard to catch in action.  The symptoms are vague and strange.  Diagnosis is only quick and easy for the very lucky and for the very unlucky who suffered for years before finding help.  If you are reading these kinds of blogs, you probably don’t fall into the former group.

3.  Because rare endocrine diseases are hard to figure out, if YOU suspect you have Cushing’s it is up to YOU to keep pushing until YOU are convinced you either have it or you don’t.  No one else is going to do that for you.  There are going to be a lot of sleepless nights and horrible symptoms and everyone else around you is going to doubt that there is something wrong with you.  Shut it out and keep digging until you are convinced you have the right answer, one way or the other.  NO ONE KNOWS YOUR BODY BETTER THAN YOU DO.  NO ONE IS GOING TO FIGURE THIS OUT FOR YOU.  That is not the way the world works.

4.  There is help out there.  Take advantage of it.  Start here:

5.  You are so much more than your appearance.

6.  Fatigue CAN be bad enough to stop you in your tracks.

7.  ‘Roid rage is real.  Really, really real.

8.  Sick, fat, tired people can also be the warmest, funniest, kindest friends.

9.  Doctors are human beings and some doctors are better than others, just like other people, just like in any other profession.